Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients
Yin-hong Zhang,
Juan Chen,
Wen-fei Mao,
Li-xi Yan,
Fei Long,
Sheng-hao Li,
Rui-xian Zhang
Affiliations
Yin-hong Zhang
Department of Medical Genetics, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, China
Juan Chen
Department of Rheumatology and Immunology, The Second Affiliated Hospital of Kunming Medical University, China
Wen-fei Mao
Department of Disease Control and Prevention, The First People's Hospital of Yunnan Province/ The Affiliated Hospital of Kunming University of Science and Technology, China
Li-xi Yan
Department of Disease Control and Prevention, The First People's Hospital of Yunnan Province/ The Affiliated Hospital of Kunming University of Science and Technology, China
Fei Long
Department of Disease Control and Prevention, The First People's Hospital of Yunnan Province/ The Affiliated Hospital of Kunming University of Science and Technology, China
Sheng-hao Li
The Third People's Hospital of Kunming/Yunnan Clinical Center for Infectious Diseases, China; Corresponding author at: The Third People's Hospital of Kunming/Yunnan Clinical Center for Infectious Diseases, No.319 Wujing Road, Guandu District, Kunming City 650041, China.
Rui-xian Zhang
Department of Disease Control and Prevention, The First People's Hospital of Yunnan Province/ The Affiliated Hospital of Kunming University of Science and Technology, China; Corresponding author at: The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, No.157 Jinbi Road, Xishan District, Kunming, Yunnan Province 650032, China.
Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disorder marked by an imbalance between pro-inflammatory Th17 cells and regulatory T cells (Tregs), which contributes to chronic inflammation and multi-organ damage, necessitating novel therapeutic strategies. Methods: This study investigates the potential of adipose-derived stem cell (ADSC) exosomes to modulate the Th17/Treg balance in SLE patients through the miR-16-5p/LATS1 axis. Flow cytometry, ELISA, and quantitative real-time PCR were utilized to assess immune cell populations and cytokine levels in SLE patients. Additionally, ADSC exosomes were isolated and characterized, and their impact on CD4+ T cells was evaluated using dual-luciferase and Western blot assays. Results: SLE patients exhibited increased Th17 cells and decreased Tregs, with corresponding changes in cytokine levels. Reduced miR-16-5p expression was noted in CD4+ T cells, correlating positively with Treg proportions. ADSC-derived exosomes were shown to deliver miR-16-5p effectively, targeting and downregulating LATS1 expression. This modulation restored the Th17/Treg balance and adjusted cytokine expression, indicating an immune regulatory effect. Conclusion: ADSC-derived exosomes, through the miR-16-5p/LATS1 axis, offer a promising therapeutic approach for SLE by restoring immune equilibrium. This study highlights the potential of exosome-based therapies in modulating immune responses, providing a foundation for developing innovative treatments for autoimmune diseases.
